Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation.

In this case-control study, the authors analyzed associations of uterine leiomyoma with atherogenic risk factors and potential sources of uterine irritation. The study included 318 case women with uterine leiomyoma that was first confirmed between 1990 and 1993 in the Baltimore, Maryland, area and 394 controls selected from women visiting the same gynecologists' offices for routine reasons. Telephone interviews were conducted with 77.8% of eligible cases and 78.0% of eligible controls. Compared with participants with no hypertension history, increased risks were observed among participants with any history of hypertension (odds ratio (OR) = 1.7; 95% confidence interval (CI): 1.0, 2.8), hypertension requiring medication (OR = 2.1; 95% CI: 1.1, 4.1), hypertension diagnosed at ages less than 35 years (for hypertension requiring medication, OR = 2.7; 95% CI: 1.0, 7.6), and hypertension of 5 or more years' duration (for hypertension requiring medication, OR = 3.1; 95% CI: 1.2, 8.2). Estimates of associations with diabetes history were very imprecise but followed similar patterns. Adjusted associations were observed with pelvic inflammatory disease (three or more episodes vs. none: OR = 3.7; 95% CI: 0.9, 15.9), chlamydial infection (history vs. no history: OR = 3.2; 95% CI: 0.8, 13.7), and use of an intrauterine device when it caused infectious complications (use vs. no use: OR = 5.3; 95% CI: 1.8, 16.3). Risk of uterine leiomyoma was also associated in a graded fashion with frequency of perineal talc use (daily use vs. no use: OR = 2.2; 95% CI: 1.4, 3.1). The authors conclude that nonhormonal factors may influence risk of uterine leiomyoma.

Contemporary management of ovarian cancer.

Major advances in treatment for epithelial ovarian cancer have occurred over the last decade, giving hope to patients and families. Surgery remains a cornerstone of therapy. In early-stage epithelial ovarian cancer, a meticulous staging procedure should be performed to aid in determining patients who require appropriate adjuvant therapy and patients who can be monitored. The patient with advanced epithelial ovarian cancer significantly benefits from aggressive cytoreductive surgery and chemotherapy, affording the patient higher rates of complete response and partial response. In the new millenium, new therapeutic modalities should enhance the current response rates.

Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer.

Difficulties in the detection, diagnosis, and treatment of ovarian cancer result in an overall low survival rate of women with this disease. A better understanding of the pathways involved in ovarian tumorigenesis will likely provide new targets for early and effective intervention. Here, we have used serial analysis of gene expression (SAGE) to generate global gene expression profiles from various ovarian cell lines and tissues, including primary cancers, ovarian surface epithelia cells, and cystadenoma cells. The profiles were used to compare overall patterns of gene expression and to identify differentially expressed genes. We have sequenced a total of 385,000 tags, yielding >56,000 genes expressed in 10 different libraries derived from ovarian tissues. In general, ovarian cancer cell lines showed relatively high levels of similarity to libraries from other cancer cell lines, regardless of the tissue of origin (ovarian or colon), indicating that these lines had lost many of their tissue-specific expression patterns. In contrast, immortalized ovarian surface epithelia and ovarian cystadenoma cells showed much higher similarity to primary ovarian carcinomas than to primary colon carcinomas. Primary tissue specimens therefore appeared to be a better model for gene expression analyses. Using the expression profiles described above and stringent selection criteria, we have identified a number of genes highly differentially expressed between nontransformed ovarian epithelia and ovarian carcinomas. Some of the genes identified are already known to be overexpressed in ovarian cancer, but several represent novel candidates. Many of the genes up-regulated in ovarian cancer represent surface or secreted proteins such as claudin-3 and -4, HE4, mucin-1, epithelial cellular adhesion molecule, and mesothelin. Interestingly, both apolipoprotein E (ApoE) and ApoJ, two proteins involved in lipid homeostasis, are among the genes highly up-regulated in ovarian cancer. Selected serial analysis of gene expression results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in archival material. These experiments provided additional evidence of the relevance of our findings in vivo. The publicly available expression data reported here should stimulate and aid further research in the field of ovarian cancer.

Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival.

OBJECTIVE: The aim of this study was to evaluate the role of cytoreductive surgery and survival determinants in patients with Stage IVB endometrial carcinoma. METHODS: All patients with Stage IVB endometrial carcinoma diagnosed between 1/1/90 and 12/31/98 were identified from tumor registry databases. Individual patient data were collected retrospectively. Survival analyses and comparisons were performed using the Kaplan-Meier method and the log-rank test. The Cox proportional hazards model was used to identify independent variables associated with survival. RESULTS: Sixty-five patients underwent surgery as primary therapy for Stage IVB endometrial carcinoma (median survival 14.8 months). The median age of the population was 65 years (range 29-85 years); 89.2% of patients were postmenopausal, and 21.5% were nulliparous. The most common histologic subtypes were endometrioid (33.8%), serous (32.3%), and mixed (16.9%). Optimal cytoreductive surgery (residual tumor < or =1 cm in maximal diameter) was accomplished in 36 patients (55.4%), while 29 patients (44.6%) were left with >1 cm residual disease. The median survival rate of patients undergoing optimal surgery was 34.3 months, a statistically significant advantage compared to patients with >1 cm residual tumor (11.0 months, P = 0.0001). Among those with optimal surgery, patients with only microscopic residual disease survived significantly longer than patients with optimal but macroscopic residual tumor. Higher performance status, age < or = 58 years, and adjuvant chemotherapy followed by radiation therapy were also significantly associated with superior survival on univariate analysis. On multivariate analysis, residual disease (P = 0.0001), performance status (P = 0.043), and age (P = 0.023) were independent predictors of survival. CONCLUSIONS: The amount of residual disease after cytoreductive surgery, age, and performance status appear to be important determinants of survival in patients with Stage IVB endometrial carcinoma. Maximal cytoreduction should be the goal at the time of primary surgery for advanced disease. For selected patients, combined postoperative chemotherapy and radiation therapy may provide some therapeutic benefit.

Cavitational ultrasonic surgical aspiration for the treatment of vaginal intraepithelial neoplasia.

OBJECTIVE: The aim of this study is to determine whether cavitational ultrasonic surgical aspiration (CUSA) is effective and safe for treating vaginal intraepithelial neoplasia (VAIN). METHODS: We conducted a retrospective chart review of 46 patients who were treated with CUSA for VAIN in a single gynecologic oncology practice between 1981 and 1999. RESULTS: At initial presentation, 39% of treated patients had grade I VAIN, 20% had grade II, and 41% had grade III. The mean duration of follow-up from initial CUSA treatment was 21 months. Twenty-nine patients (63%) were initially treated with CUSA, 7 patients (15%) with laser vaporization, 7 patients (15%) with surveillance by Papanicolaou smear, 1 patient (2%) with partial vaginectomy, 1 patient (2%) with 5-fluorouracil, and 1 patient (2%) with loop excision. Patients initially treated with CUSA had a higher percentage of grade III VAIN at diagnosis (48%) than did patients initially treated with other methods (29%). A significantly greater proportion of patients initially treated with CUSA had no recurrence of VAIN (66%) compared with patients initially treated with other methods (0%) (P < 0.0001). A significantly greater proportion of patients who were treated for recurrent disease with CUSA had no further recurrence (52%) compared with patients treated for recurrent disease with other methods (9%) (P < 0.001). No patient treated with CUSA reported adverse effects; 7 patients treated with other methods reported dysuria, burning, and pain. CONCLUSION: These initial data suggest that CUSA is a safe and effective method for treating VAIN and may be an appropriate treatment for many patients.

Use of the ultrasound surgical aspirator in ovarian cancer: a case-control study.

BACKGROUND: This study was undertaken to evaluate the use of the ultrasound surgical aspirator in ovarian cancer and to determine if cytoreduction was improved with its use. METHODS: The study is a retrospective case control trial. Twenty-six consecutive ovarian cancer patients who had the ultrasound surgical aspirator used during their surgery were retrospectively compared to 25 consecutive ovarian cancer patients who did not have the ultrasound surgical aspirator used during their surgeries. The latter group had their surgeries immediately before the ultrasound surgical aspirator was introduced into the hospital. Both groups were similar in age, stage, histology type, grade, and median number of chemotherapy cycles. RESULTS: Patients that had the ultrasound surgical aspirator used had a 69% optimal cytoreduction rate compared to 16% in the control group (p = .001). This was statistically significant (p = 0.001). Survival time was equal in both groups. CONCLUSIONS: Results of the study showed that use of the ultrasound surgical aspirator may permit more patients to be optimally cytoreduced.

The use of paclitaxel and cisplatin in a patient with epithelial ovarian cancer and human immunodeficiency virus.

OBJECTIVE: Several spots exist of human immunodeficiency virus (HIV)-positive patients developing epithelial ovarian cancer. The optimal chemotherapeutic regimen has been unclear due to potential immunotoxicity from chemotherapy in these already immunocompromised patients. This is the first report of paclitaxel-based combination chemotherapy in an HIV-positive patient with ovarian cancer. METHOD: A 39-year-old woman with HIV was diagnosed with poorly differentiated serous carcinoma. She underwent optimal cytoreductive surgery and received six courses of paclitaxel and cisplatin. RESULTS: The patient experienced a complete clinical response to therapy with no adverse effect on surrogate markers for human immunodeficiency virus (CD4 count, beta2 microglobulin, neopterin, p24 antigen, and viral load). CONCLUSION: Paclitaxel- and platinum-based chemotherapy, the standard of care for adjuvant chemotherapy in advanced ovarian carcinoma, is appropriate therapy for ovarian cancer patients with HIV. There is no evidence that the paclitaxel/cisplatin regimen is associated with progression of HIV or increased chemotherapy-associated morbidity.

Extraovarian granulosa cell tumor.

OBJECTIVE: The aim of this study was to report a case of extraovarian granulosa cell tumor and to describe its relevance to the histologic origin of granulosa cell tumors and to clinical practice. METHODS: The clinical course and histopathology of the case were reviewed, and a literature search for other reported cases was performed. RESULTS: A 67-year-old woman presented with postmenopausal bleeding and a pelvic mass. Laparotomy revealed a 16-cm mass arising from the right pelvic sidewall, filling the pelvis, and involving the bladder and rectosigmoid colon. Both ovaries appeared normal and were separate from the mass. Pathologic examination revealed granulosa cell tumor. A literature search revealed no recently reported cases of extraovarian granulosa cell tumor. CONCLUSIONS: Granulosa cell tumors can arise in locations other than the ovary and may be derived from the mesenchyme of the genital ridge. Women who have undergone oophorectomy may have the potential to develop granulosa cell tumors.

Vulvar porokeratosis: case report and review of the literature.

We report the first case of vulvar porokeratosis that occurred in a 39-year-old woman with a 30-year history of vulvar pruritus and disfiguring vulvar lesions. Ultrasonic surgical aspiration resulted in resolution of her pruritus and excellent cosmesis. Light microscopy revealed characteristic cornoid lamellae and electron microscopy confirmed the diagnosis of vulvar porokeratosis.

Serum CA-125 screening for ovarian cancer in patients with dermatomyositis.

Ovarian cancer is the most overrepresented malignancy diagnosed in women with dermatomyositis. Unfortunately, screening with pelvic examination rarely detects this cancer prior to the development of metastatic disease. Our objective was to examine the use of serum CA-125 antigen levels in screening patients with dermatomyositis for ovarian cancer. A single blinded, case-control study was conducted in our institution of CA-125 levels in 14 women diagnosed with dermatomyositis between 1986 and 1993, 4 of whom subsequently developed ovarian cancer. In the 4 patients who developed ovarian cancer ("cases"), CA-125 determinations were performed on serum stored 5 to 19 months prior to the diagnosis of ovarian cancer. In the remaining 10 patients ("controls"), serum was drawn for CA-125 level determination at the time of the study, and simultaneous gynecologic and endovaginal ultrasound examinations were performed to exclude clinical evidence of ovarian cancer. All CA-125 serum measurements were performed simultaneously by a technician blinded to disease status using one diagnostic kit. CA-125 was found to be elevated in 2 patients with ovarian cancer (on serum obtained 5 and 13 months prior to the date of diagnosis of ovarian cancer) and in none of the control patients without clinical or ultrasound evidence of ovarian cancer (relative risk = 20, 95% confidence interval = [0.64, 666]). In these 14 patients, the sensitivity of CA-125 elevation for detection of ovarian cancer was 50%, and specificity was 100%. Serum CA-125 screening for ovarian cancer in patients having dermatomyositis may be useful; however, prospective studies are needed to confirm this and to determine the effect of screening on cancer stage at diagnosis and long-term survival.

Gynecologic oncology patients in the surgical ICU. Impact on outcome.

OBJECTIVE: To determine the risk factors and outcome for survival of gynecologic oncology patients in the surgical intensive care unit (SICU). STUDY DESIGN: A chart review from January 1987 through May 1992 yielded 73 gynecologic oncology patients with a malignancy who had undergone surgery with a minimum stay of three days in the SICU. Of these 73 patients, 49 patients died of malignancy, 5 were alive with disease, and 19 were alive without evidence of disease. RESULTS: The median survival of the 73 patients was 123 days; that of 48 ovarian cancer patients was 50 days. Twenty patients (27.4%) died in the hospital. CONCLUSION: This study, with multivariate analysis, showed that multiple medical conditions, especially cardiac disease, and a stay of longer than five days in the SICU had a significant impact on survival, with ovarian cancer patients staying longer and having poorer survival. These results will help in triaging patients for postsurgical management.

Prolonged stays of OB/GYN patients in the surgical intensive care unit. A cost-benefit analysis.

OBJECTIVE: To delineate costs between various obstetric and gynecologic (OB/GYN) patients with stays in the surgical intensive care unit (SICU). STUDY DESIGN: A chart review identified 86 OB/GYN patients who had a minimum SICU stay of three days between January 1987 and May 1992. RESULTS: Our study showed that the total cost of these cases was $3,344,010, with a median of $29,780 (range, $20,230-180,610) and that the difference between patients with malignancies and those without (median, $20,340) was not statistically significant (P = .11). However, cases of malignant disease that had either a prexisting medical condition or an SICU stay of more than five days cost more than any other cases (P = .038). The SICU share of total hospital cost ranged from 20.7% in patients with malignancy to 40% in patients without malignancy. CONCLUSION: As health care costs come under closer scrutiny, the critically ill patient should not be placed at risk of lessened chances of survival because perceived savings result in decreasing quality of care.

Dermatomyositis sine myositis: association with malignancy.

OBJECTIVE: To describe dermatomyositis (DM) sine myositis as a distinct diagnostic subclass of DM and the association with malignancy. METHODS: This case series includes all patients presenting to our primary and tertiary care outpatient dermatology department with DM and DM sine myositis between 1986 and 1993. Seven patients were diagnosed with classic DM and 12 with DM sine myositis. We analyzed average age of onset, duration of followup, clinical course, and incidence of associated malignancy in the patients with classic DM and DM sine myositis. RESULTS: No statistically significant differences were found in these 2 groups on examining age at onset and frequency of associated malignancy. Malignancy was diagnosed in 4 of 12 (25%) patients with DM sine myositis followed for a total of 50.8 patient-years (average followup 51 months) and in 2 of 7 (28%) patients with classic DM followed for a total of 20.6 patient-years (average followup 35 months). CONCLUSION: Although these patients with DM are select and few, they demonstrate that DM sine myositis may be quite similar to classic DM. It may be said that like DM, DM sine myositis may represent a paraneoplastic syndrome. DM sine myositis should be added to the currently accepted polymyositis/dermatomyositis classification system, with appropriate emphasis on the potential association with malignancy.

Adequacy of conization margins in adenocarcinoma in situ of the cervix as a predictor of residual disease.

In this retrospective analysis, 18 patients with adenocarcinoma in situ (AIS) of the cervix diagnosed on cervical conization between April 1988 and June 1994 were identified. The margins of all specimens were assessed for disease involvement. If hysterectomy or repeat conization was performed, the presence of AIS in the specimen was ascertained. Eleven of 18 conizations (61%) had AIS with negative margins of resection. Two of these 11 patients (18%) were followed conservatively and have had negative Pap smears for a mean of 1.7 years. The remaining 9 patients (82%) were treated by hysterectomy, with 4 (44%) showing residual AIS in the final surgical specimen. Six of the 18 conizations (33%) had positive margins for AIS. Five of these patients (83%) were treated with hysterectomy and one patient was treated with a repeat conization. Three of the five hysterectomy specimens as well as the repeat conization specimen (67%) contained residual AIS. One conization (6%) had margins that could not be assessed. The absence of residual AIS in the final surgical specimen was not predicted by the negative margin status on the conization.

Endometrial blood flow analysis in postmenopausal women: can it help differentiate benign from malignant causes of endometrial thickening?

PURPOSE: To determine if prominent vascularity and low pulsatility index (PI) and resistive index (RI) in endometrial arteries help differentiate carcinoma from benign lesions. MATERIALS AND METHODS: Forty-five postmenopausal women with at least 8-mm-thick endometrium at endovaginal ultrasound (US) underwent color duplex Doppler endovaginal US of the endometrium. PI and RI values were recorded from arterial waveforms generated in areas of increased vascularity. RESULTS: At color duplex Doppler endovaginal US, endometrial arterial flow was seen in 23 of 36 (64%) proved benign endometrial lesions. The range of PIs for benign lesions was 0.31-1.77 (mean, 0.72 +/- 0.33 [standard deviation]) and for RIs was 0.27-0.84 (mean, 0.48 +/- 0.13). Arterial vessels were seen in five of nine proved endometrial cancers (56%); the range of PIs was 0.42-1.17 (mean, 0.71 +/- 0.32) and for RIs was 0.34-0.69 (mean, 0.48 +/- 0.15). Differences in mean PI and RI for benign and malignant lesions were not significant. CONCLUSION: Low-impedance arterial flow is observed in various diseases of the endometrium, and there is an overlap between the PI and RI of benign and malignant lesions.

Report of three new cases of squamous carcinoma of the endometrium with emphasis in the HPV status.

Primary squamous cell carcinoma of the endometrium is exceedingly rare. Only 31 cases that fulfill Fluhmann's criteria have been reported in the literature. We report three cases of primary squamous cell carcinoma of the endometrium. In two of the three cases, estrogen receptor (ER) and progesterone receptor (PR) status were analyzed. Only one case contained ER/PR. Additionally, in situ hybridization was performed to determine the presence of human papillomavirus (HPV) in these cases. HPV was not detected in these three cases of primary squamous cell carcinoma of the endometrium.

Premarin-induced ischemic colitis.

There are numerous literature reports of oral contraceptive-induced (estrogen and progesterone) ischemic bowel disease. However, Premarin-induced (equine conjugated estrogen) intestinal ischemia has rarely been reported. We describe three cases of Premarin-induced ischemic colitis. In contrast to oral contraceptive-induced ischemic colitis, Premarin-induced ischemia is restricted to the colon, has not required surgical therapy, can have a chronic or chronic intermittent course, may be reversible despite continued usage of Premarin, and may present with nonspecific abdominal and colonic symptoms.

Selective vascular embolization in benign gynecologic conditions.

Eight patients with benign obstetric and gynecologic conditions required embolization. There was a total of 11 embolizations, and embolizing agents were chosen depending on the abnormality requiring embolization. Gelfoam, Ivalon and alcohol were used to treat vascular malformations. Ovarian veins were embolized with coils. Postoperative bleeding was managed with Gelfoam, coils and/or Ivalon. Four patients had bleeding after hysterectomy or vaginal suspension. One patient had postdelivery bleeding. All the bleeding was controlled after embolization. A uterine arteriovenous malformation was managed with embolization, allowing the patient to carry her next pregnancy to term. The symptoms of a vulvar hemangioma and ovarian syndrome were controlled with vascular embolization. Morbidity was minimal. Embolization is the primary treatment of choice in obstetric and gynecologic patients with postoperative bleeding or symptomatic vascular malformation.

Ovarian cancer in patients with dermatomyositis.

A consensus regarding adequate screening to detect early malignancy in the setting of dermatomyositis (DMM) has yet to be reached. This issue is particularly relevant with regard to ovarian cancer, as early detection with routine examinations, ultrasound, and abdominal CT may not be successful. Four of 15 women diagnosed with and seen in our department for DMM between 1986 and 1993 were subsequently diagnosed with metastatic papillary serous ovarian carcinoma. One additional patient developed metastatic pelvic papillary adenocarcinoma, believed to be of ovarian origin. These diagnoses of advanced cancer were unexpected, as all women had undergone repeated cancer screenings beyond what is normally recommended for patients with DMM. The 5 women were strikingly similar in their initial presentations and subsequent courses. In each, the diagnosis of DMM was delayed from 2 to 10 months, as they were initially misdiagnosed with a photoinduced or contact dermatitis. All except 1 had severe, recalcitrant skin disease despite attempted therapy with antimalarial and immunosuppressive agents. All 4 patients who survived the postoperative period after tumor debulking showed either improvement or resolution of their DMM. It appears that women with DMM have an increased incidence of ovarian cancer, which is usually diagnosed months to a few years (range, 0 d to 6 y) after DMM has been diagnosed. Although recommendations have been made regarding cancer screening in these individuals, recommendations for initial and surveillance examinations vary from routine history and physical examination to evaluations including extensive radiologic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)